The interaction of α° thalassaemia with Hb Icaria: three unusual cases of haemoglobinopathy H

Abstract

The clinical, haematological, biosynthetic and molecular data of three Greek haemoglobin H (HbH) disease patients with a distinctive clinical phenotype are described. During infancy all three patients had unusually severe clinical manifestations for HbH disease, with anaemia necessitating blood transfusions, signs of bone changes, growth impairment, and splenomegaly. Molecular analysis identified a rare alpha-thalassaemia genotype (--Med/ alpha Ic alpha). Splenectomy resulted in marked amelioration of the clinical signs; post splenectomy all three patients preserve adequate haemoglobin levels (9-10 g/dl) with growth restored to normal. Despite the initial severe clinical phenotype in these patients, our experience indicates that splenectomy modifies the clinical course to that of mild thalassaemia intermedia. This observation should be considered carefully when giving genetic counselling to families carrying the rare Hb Icaria mutation and an alpha zero thalassaemia mutation.

Phenotypic and molecular diversity of haemoglobin H disease: a Greek experience

“…The null α 0 deletions are most severe and non‐deletion mutations are considered to have an intermediate severity between α + and α 0 deletions. Although globin chain synthesis ratios in 22 Hb H patients did not clearly reflect α‐globin chain output expected from underlying genotypes (even excluding three cases with chain termination mutants who had α/non‐α synthesis ratios of 0·6), clinical and haematological findings were generally consistent with the expected order of increasing severity of HbH disease genotypes (–α/α T α, –α/α 0 , and α T α/α 0 or α T α/α T α), confirming a strong correlation of Hb H disease phenotypes with genotypes, as previously found in this and other populations (Galanello et al , 1983; Paglietti et al , 1986; Fucharoen et al , 1988; Kattamis et al , 1988; Kanavakis et al , 1996).…”

“…Four of the Hb Icaria‐Hb H patients followed a severe clinical course with a need for regular blood transfusions from infancy. Three patients (8, 9 and 10), were splenectomized at 6–7 years, after which their anaemia and subsequent clinical course markedly improved (Kanavakis et al , 1996), but the fourth case (patient 7), presently 24‐years‐old, has not been splenectomized and still requires monthly blood transfusions. Paradoxically, the brother of patient 7 (patient 6), and one other case (patient 11), have an intermediate clinical course, maintaining haemoglobin levels above 8·0 g/dl without transfusions (Fig 1, patient 6), and with moderate splenomegaly (Table II).…”

“…Disease severity can be largely attributed to the degree of α‐chain deficiency, which, in turn, is related to the underlying α‐thalassaemia genotypes. Correlation of phenotypes with genotypes in Hb H disease has been previously demonstrated in Greece (Kanavakis et al , 1996; Kattamis et al , 1988) and several other populations (Galanello et al , 1983; Paglietti et al , 1986; Fucharoen et al , 1988), but, in these studies, patient numbers and/or Hb H genotypes were relatively limited for comparison. The wide spectrum of α‐thalassaemia determinants in Greece (Kattamis et al , 1988; Traeger‐Synodinos et al , 1993, 1998; Kanavakis et al , 1996), apparently greater than in any other population studied to date (Galanello et al , 1992; Baysal et al , 1995; Tamary et al , 1998), gives rise to a large number of Hb H disease genotypes.…”

Hemoglobin H disease: not necessarily a benign disorder

“…22,31,[61][62][63] In patients with marked splenomegaly and hypersplenism, splenectomy can result in highly significant hematologic and clinical improvements. 127 Postoperative complications include septicemia, deep venous thrombosis, and pulmonary embolism. 128,129 Cholecystectomy may have to be done whenever surgically indicated.…”

Hb H disease resulting from the association of an αº-thalassemia allele [-(α)20.5] with an unstable α-globin variant [Hb Icaria]: first report on the occurrence in Brazil

“…Hb Icaria is a rare Hb structural and thalassemic variant described in Greek, Yugoslavian and Macedonian families (Clegg et al , 1974; Efremov et al , 1990; Kanavakis et al , 1996). It is difficult to detect in peripheral blood samples by the more commonly used techniques, due to its very low concentration and electrophoretic mobility, which is slower than that of Hb A 2 at alkaline pH (Clegg et al , 1974).…”